Vastarel MR

Trimetazidine

Name of the medicinal product

Vastarel MR, modified release film-coated tablets in 10's and 60's / box.

Qualitative and quantitative composition
Trimetazidine dihydrochloride 35 mg

Excipients q.s. for one modified release film-coated tablet

Pharmacological properties
• Pharmacodynamic properties

Other cardiovascular antianginal drug Code ATC: C01EB15
(C: cardiovascular system)
By preserving energy metabolism in cells exposed to hypoxia or ischaemia, trimetazidine prevents a decrease in intracellular ATP levels, thereby ensuring the proper functioning of ionic pumps and transmembrane sodium-potassium flow whilst maintaining cellular homeostasis.

In animals
Trimetazidine:
  - helps maintain energy metabolism in the heart and neurosensory organs during episodes of ischaemia and hypoxia,
  - reduces intracellular acidosis and alterations in transmembrane ion flow caused by ischaemia,
  - decreases the migration and infiltration of polynuclear neutrophils in ischaemic and reperfused cardiac tissue. It also reduces the size of experimental infarctions,

  - exerts this action in the absence of any direct haemodynamic effect.

In man
Controlled studies in angina patients have shown that trimetazidine:
  - increases coronary flow reserve, thereby delaying the onset of exercise-induced ischaemia, starting from the 15th day of treatment,
  - limits rapid swings in blood pressure without any significant variations in heart rate,

  - significantly decreases the frequency of angina attacks,
  - leads to a significant decrease in the use of trinitroglycerin.

In a two-month study in patients receiving 50 mg atenolol, adding one 35 mg trimetazidine modified release tablet produced a significant increase in the time to 1-mm ST-segment depression in exercise tests, when compared to a placebo, 12 hours after taking the drug.

• Pharmacokinetic properties

  - After oral administration, maximum concentration is found, on average, 5 hours after taking the tablet. Over 24 hours the plasma concentration remains at levels above or equal to 75% of the maximum concentration for 11 hours.

Steady state is reached by the 60th hour, at the latest.
  - The pharmacokinetic characteristics of Vastarel MR are not influenced by meals.
  - The apparent distribution volume is 4.8 I/kg; protein binding is low: in vitro measurements give value of 16%.
  - Trimetazidine is eliminated primarily in the urine, mainly in the unchanged form. The elimination half-life of Vastarel MR is an average of 7 hours in healthy young volunteers and 12 hours in subjects aged more than 65 years. Total clearance of trimetazidine is the result of major renal clearance which is directly correlated to creatinine clearance and, to a lesser extent, to liver clearance which is reduced with age.
  - A specific clinical study carried out in an elderly population using a dosage of 2 tablets per day taken in 2 doses, analysed by a kinetic population method, showed an increase in plasma exposure which does not justify a dosage alteration.
 

Therapeutic indications
  - Prophylactic treatment of episodes of angina pectoris.
  - Adjuvant symptomatic treatment of vertigo and tinnitus.
  - Adjuvant treatment of the decline in visual acuity and visual field disturbances presumably of vascular origin.

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

The use of this medicinal product is not recommended during pregnancy and breast-feeding (see section Pregnancy and lactation)
 

Special warnings and precautions for use

This drug is not a curative treatment for angina attacks, nor is it indicated as an initial treatment for unstable angina, or myocardial infarction. In the event of an angina attack, the coronaropathy should be reevaluated and an adaptation of the treatment considered (drug treatment and possibly revascularisation).

Pregnancy & breast-feeding
Pregnancy:
No teratogenic effect was seen in animal studies; in the absence of clinical data, a risk of birth defect induction cannot be excluded;
consequently, as a precaution, it is best not to prescribe the drug during pregnancy.

Lactation:
In the absence of data on excretion of the drug in milk, breast-feeding is not recommended during treatment.

Side effects
Rare cases of gastrointestinal disorders (nausea and vomiting).

Interaction with other medicinal products and other forms of interaction
No drug interaction has been reported; in particular, trimetazidine can be prescribed in combination with heparin, calciparin, vitamin K antagonist, oral hypolipidaemia agents, aspirin, beta-blockers, calcium inhibitors, digitalis (Trimetazidine has no effect on the plasma levels of digoxin).

Dosage and method of administration
One tablet at mealtimes in the morning and evening.

Overdosage
The experience of overdosage is very limited. Patients should be monitored in terms of cardiovascular and hemodynamic parameters.

Storage conditions
No special storage condition required. Store below 30°C.